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Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model

BACKGROUND: Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have been proposed as an alternative to cell therapy, creating new possible delivery modalities such as nebulisation. We wished to investigate the therapeutic potential of directly nebulised MSC-EVs in the mitigation of Esc...

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Autores principales: Gonzalez, Hector, McCarthy, Sean, Masterson, Claire, Byrnes, Declan, Sallent, Ignacio, Horan, Emma, Elliman, Stephen J., Vella, Gabriele, Prina-Mello, Adriele, Silva, Johnatas D., Krasnodembskaya, Anna D., MacLoughlin, Ronan, Laffey, John G., O’Toole, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245544/
https://www.ncbi.nlm.nih.gov/pubmed/37280647
http://dx.doi.org/10.1186/s13287-023-03385-6
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author Gonzalez, Hector
McCarthy, Sean
Masterson, Claire
Byrnes, Declan
Sallent, Ignacio
Horan, Emma
Elliman, Stephen J.
Vella, Gabriele
Prina-Mello, Adriele
Silva, Johnatas D.
Krasnodembskaya, Anna D.
MacLoughlin, Ronan
Laffey, John G.
O’Toole, Daniel
author_facet Gonzalez, Hector
McCarthy, Sean
Masterson, Claire
Byrnes, Declan
Sallent, Ignacio
Horan, Emma
Elliman, Stephen J.
Vella, Gabriele
Prina-Mello, Adriele
Silva, Johnatas D.
Krasnodembskaya, Anna D.
MacLoughlin, Ronan
Laffey, John G.
O’Toole, Daniel
author_sort Gonzalez, Hector
collection PubMed
description BACKGROUND: Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have been proposed as an alternative to cell therapy, creating new possible delivery modalities such as nebulisation. We wished to investigate the therapeutic potential of directly nebulised MSC-EVs in the mitigation of Escherichia coli-induced pneumonia. METHODS: EV size, surface markers and miRNA content were assessed pre- and post-nebulisation. BEAS2B and A459 lung cells were exposed to lipopolysaccharide (LPS) and treated with nebulised bone marrow (BM) or umbilical cord (UC) MSC-EVs. Viability assays (MTT) and inflammatory cytokine assays were performed. THP-1 monocytes were stimulated with LPS and nebulised BM- or UC-EVs and phagocytosis activity was measured. For in vivo experiments, mice received LPS intratracheally (IT) followed by BM- or UC-EVs intravenously (IV) and injury markers assessed at 24 h. Rats were instilled with E. coli bacteria IT and BM- or UC-EVs delivered IV or by direct nebulisation. At 48 h, lung damage was assessed by physiological parameters, histology and inflammatory marker presence. RESULTS: MSC-EVs retained their immunomodulatory and wound healing capacity after nebulisation in vitro. EV integrity and content were also preserved. Therapy with IV or nebulised MSC-EVs reduced the severity of LPS-induced lung injury and E. coli-induced pneumonia by reducing bacterial load and oedema, increasing blood oxygenation and improving lung histological scores. MSC-EV treated animals also showed lower levels of inflammatory cytokines and inflammatory-related markers. CONCLUSIONS: MSC-EVs given IV attenuated LPS-induced lung injury, and nebulisation of MSC-EVs did not affect their capacity to attenuate lung injury caused by E. coli pneumonia, as evidenced by reduction in bacterial load and improved lung physiology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03385-6.
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spelling pubmed-102455442023-06-08 Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model Gonzalez, Hector McCarthy, Sean Masterson, Claire Byrnes, Declan Sallent, Ignacio Horan, Emma Elliman, Stephen J. Vella, Gabriele Prina-Mello, Adriele Silva, Johnatas D. Krasnodembskaya, Anna D. MacLoughlin, Ronan Laffey, John G. O’Toole, Daniel Stem Cell Res Ther Research BACKGROUND: Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have been proposed as an alternative to cell therapy, creating new possible delivery modalities such as nebulisation. We wished to investigate the therapeutic potential of directly nebulised MSC-EVs in the mitigation of Escherichia coli-induced pneumonia. METHODS: EV size, surface markers and miRNA content were assessed pre- and post-nebulisation. BEAS2B and A459 lung cells were exposed to lipopolysaccharide (LPS) and treated with nebulised bone marrow (BM) or umbilical cord (UC) MSC-EVs. Viability assays (MTT) and inflammatory cytokine assays were performed. THP-1 monocytes were stimulated with LPS and nebulised BM- or UC-EVs and phagocytosis activity was measured. For in vivo experiments, mice received LPS intratracheally (IT) followed by BM- or UC-EVs intravenously (IV) and injury markers assessed at 24 h. Rats were instilled with E. coli bacteria IT and BM- or UC-EVs delivered IV or by direct nebulisation. At 48 h, lung damage was assessed by physiological parameters, histology and inflammatory marker presence. RESULTS: MSC-EVs retained their immunomodulatory and wound healing capacity after nebulisation in vitro. EV integrity and content were also preserved. Therapy with IV or nebulised MSC-EVs reduced the severity of LPS-induced lung injury and E. coli-induced pneumonia by reducing bacterial load and oedema, increasing blood oxygenation and improving lung histological scores. MSC-EV treated animals also showed lower levels of inflammatory cytokines and inflammatory-related markers. CONCLUSIONS: MSC-EVs given IV attenuated LPS-induced lung injury, and nebulisation of MSC-EVs did not affect their capacity to attenuate lung injury caused by E. coli pneumonia, as evidenced by reduction in bacterial load and improved lung physiology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03385-6. BioMed Central 2023-06-06 /pmc/articles/PMC10245544/ /pubmed/37280647 http://dx.doi.org/10.1186/s13287-023-03385-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Gonzalez, Hector
McCarthy, Sean
Masterson, Claire
Byrnes, Declan
Sallent, Ignacio
Horan, Emma
Elliman, Stephen J.
Vella, Gabriele
Prina-Mello, Adriele
Silva, Johnatas D.
Krasnodembskaya, Anna D.
MacLoughlin, Ronan
Laffey, John G.
O’Toole, Daniel
Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model
title Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model
title_full Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model
title_fullStr Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model
title_full_unstemmed Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model
title_short Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model
title_sort nebulised mesenchymal stem cell derived extracellular vesicles ameliorate e. coli induced pneumonia in a rodent model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245544/
https://www.ncbi.nlm.nih.gov/pubmed/37280647
http://dx.doi.org/10.1186/s13287-023-03385-6
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